Cosmetic preparations containing photostable UV-A filters

ABSTRACT

A sunscreen-containing cosmetic formulation to protect the human epidermis from UV light in the range from 280 to 400 nm, which formulation includes a cosmetically suitable carrier, together with compounds which absorb in the UV-B region and as photostable UV-A filters effective amounts of compounds of the formula I as defined in the specification.

DESCRIPTION

The invention relates to the use of substituted diphenylmalononitrilesas photostable UV-A filters in cosmetic formulations to protect thehuman epidermis from UV radiation, specifically in the range from 320 to400 nm.

The sunscreen agents employed in cosmetic formulations have the task ofpreventing harmful effects of sunlight on the human skin or at leastreducing their consequences. In addition, however, these sunscreenagents also serve to protect other ingredients from decomposition ordegradation by UV radiation.

The sunlight reaching the surface of the earth contains UV-B (280 to 320nm) and UV-A (>320 nm), radiation which is immediately adjacent to thevisible light region. The effect on the human skin, especially of UV-Bradiation, is manifested by sunburn. Accordingly the industry suppliesquite a large number of substances which absorb UV-B radiation and thusprevent sunburn.

Dermatological investigations have now shown that UV-A radiation is alsoperfectly able to cause skin damage by, for example, damaging thekeratin or elastin. This results in a reduction in the elasticity andwater-storage capacity of the skin, ie. the skin becomes less supple andis prone to wrinkles. The noticeably high incidence of skin cancer inregions exposed to strong sunlight shows that evidently damage to thegenetic information in the cells is also caused by sunlight,specifically by UV-A radiation. All these findings therefore make itappear necessary to develop efficient filter substances for the UV-Aregion.

There is a growing need for sunscreen agents for cosmetic formulationswhich can be used in particular as UV-A filters and whose absorptionmaxima should therefore be in the region from about 320 to 380 nm. Inorder to achieve the desired effect with use of the minimum amount,sunscreen agents of this type should additionally have a highly specificextinction. In addition, sunscreen agents for cosmetic products mustalso meet a large number of other requirements, for example goodsolubility in cosmetic oils, high stability of the emulsions producedwith them, toxicological acceptability and little intrinsic odor andcolor.

Another requirement which must be met by sunscreen agents is adequatephotostability. However, this is only inadequately ensured, if at all,with UV-A absorbing sunscreen agents available to date.

French patent No. 2 440 933 describes4-(1,1-dimethylethyl)-4'-methoxydibenzoylmethane as UV-A filter. Theproposal is to combine this specific UV-A filter, which is sold byGIVAUDAN under the name "PARASOL 1789", with various UV-B filters inorder to absorb all UV rays with a wavelength from 280 to 380 nm.

However, this UV-A filter has insufficient photochemical stability, whenused alone or in combination with UV-B filters, to ensure permanentprotection of the skin during lengthy exposure to the sun, which makesrepeated applications at regular and short intervals necessary ifeffective protection of the skin from all the UV rays is desired.

This is why, according to EP 0514491, the UV-A filters with inadequatephotostability are to be stabilized by adding2-cyano-3,3-diphenylacrylic esters which themselves act as filters inthe UV-B region.

It is an object of the present invention to propose sunscreen agents forcosmetic purposes which absorb in the UV-A region and are photostable.

We have found that this object is achieved by adding compounds of theformula I ##STR1## where R¹ and R² are identical or differentstraight-chain or branched aliphatic or cycloaliphatic radicals whichare in the para and/or ortho position and have 1 to 18 carbon atoms, andwhere R¹ can additionally be a hydrogen atom, and where furthermore n is1 or 2, when these compounds have their essential absorption in therange from 320 to 380 nm, as UV-A filters in cosmetic formulations toprotect the human skin from the sun's rays, together with compoundswhich absorb in the UV-B region and are known per se for cosmeticformulations.

Aliphatic and cycloaliphatic radicals mean in particular hydrocarbonradicals which may be interrupted by oxygen atoms.

It is preferred in this connection to use compounds of the formula I##STR2## where R¹ and R² are identical or different and arestraight-chain or branched alkyl radicals having 1 to 18 carbon atoms,in which the alkyl chain can be interrupted by oxygen atoms, and whereR¹ can also be hydrogen, and n is 1 and 2.

Particularly suitable compounds of the formula I are those where R¹ andR² are identical or different branched alkoxy radicals which are in thepara position and have 3 to 12 carbon atoms, and n is in each case 1,and R¹ can also be hydrogen.

Particularly preferred individual compounds are the following, where R¹and/or R² are in the para position and are

    ______________________________________                                        n-propoxy          isopropoxy                                                   n-butoxy 1-methylpropoxy                                                      2-methylpropoxy n-pentoxy                                                     1,1-dimethylpropoxy 3-methylbutoxy                                            hexoxy 2,2-dimethylpropoxy                                                    heptoxy 1-methyl-1-ethylpropoxy                                               2-ethylhexoxy and/or octoxy,                                                ______________________________________                                    

and where R¹ can also be hydrogen.

The compounds which can be used according to the invention areexpediently prepared in a manner known per se by a process disclosed byGeorges Charles, Bull.Soc.Chim. 1962, 1559, in which benzophenone isreplaced as starting compounds by the corresponding imines of theformula II ##STR3## where R¹ and R² and n have the meanings indicatedabove, with malononitrile in polar organic solvents with exclusion ofwater.

This process has several advantages: no catalyst is required; the yieldsare better and the reaction takes place at lower temperatures. Thestarting compounds of the formula II can be obtained, for example, bythe process of DE-A 4442138.

Sunscreen-containing cosmetic formulations are, as a rule, based on acarrier which contains at least one oil phase. However, formulationsonly with an aqueous (gel) base are also possible. Accordingly, oils,oil-in-water and water-in-oil emulsions, creams and pastes, protectivelipstick bases or gels are suitable.

Sunscreen products of these types can accordingly be in liquid, pasty orsolid form, for example as water-in-oil creams, oil-in-water creams andlotions, aerosol foam creams, gels, oils, grease pencils, dustingpowders, sprays or alcoholic/aqueous solutions.

Examples of conventional oil components in cosmetics are liquidparaffin, glyceryl stearate, isopropyl myristate, diisopropyl adipate,acetylstearyl 2-ethylhexanoate, hydrogenated polyisobutene, petrolatum,caprylic acid/capric acid triglycerides, microcrystalline wax, lanolinand stearic acid.

Examples of conventional cosmetic auxiliaries which may be suitable asadditives are emulsifiers such as fatty alcohol ethoxylates, sorbitanfatty acid esters or lanolin derivatives, thickeners such ascarboxymethylcellulose or crosslinked polyacrylic acid, preservativesand perfumes. Finally, other substances which absorb in the UV-A regionand are known per se can also be used if they are stable in the completesystem of the combination of UV-B and UV-A filters to be used accordingto the invention.

The present invention furthermore relates to cosmetic formulations whichcomprise 0.1 to 10% by weight, preferably 1 to 7% by weight, based onthe total amount of the cosmetic formulation, of one or more of thecompounds of the formula I together with compounds which absorb in theUV-B region and are known per se for cosmetic formulations as sunscreenagents, with the compounds of the formula I usually being employed in asmaller amount than the UV-B-absorbing compounds.

Most of the sunscreen agents in the cosmetic formulations used toprotect the human epidermis comprise compounds which absorb UV light inthe UV-B region, ie. in the range from 280 to 320 nm. Examples ofcontents of the UV-A absorbers to be used according to the invention arefrom 10 to 90% by weight, preferably 20 to 50% by weight, based on thetotal amount of UV-B- and UV-A-absorbing substances.

Any UV-B filter substances are suitable as UV-B filter substances usedin combination with the compounds of the formula I to be used accordingto the invention. Examples which may be mentioned are:

    ______________________________________                                                                       CAS No.                                          No. Substance (=acid)                                                       ______________________________________                                         1   4-Aminobenzoic acid       150-13-0                                          2 3-(4'Trimethylammonium)benzylidenebornan-2-one 52793-97-2                   methyl sulfate                                                                3 3,3,5-Trimethylcyclohexyl salicylate 118-56-9                               (Homosalatum)                                                                 4 2-Hydroxy-4-methoxybenzophenone 131-57-7                                    (Oxybenzonum)                                                                 5 2-Phenylbenzimidazole-5-sulfonic acid and its 27503-81-7                    potassium, sodium and triethanolamine salts                                   6 3,3'-(1,4-Phenylenedimethine)-bis(7,7-dimethyl- 90457-82-2                  2-oxobicyclo[2.2.1]heptane-1-methanesulfonic                                  acid) and its salts                                                           7 Polyethoxyethyl 4-bis(polyethoxy)aminobenzoate 113010-52-9                  8 2-Ethylhexyl 4-dimethylaminobenzoate 21245-02-3                             9 2-Ethylhexyl salicylate 118-60-5                                           10 2-Isoamyl 4-methoxycinnamate 7/6/7-10-2                                    11 2-Ethylhexyl 4-methoxycinnamate 5466-77-3                                  12 2-Hydroxy-4-methoxybenzophenone-5-sulfone 4065-45-6                         (Sulisobenzonum) and the sodium salt                                         13 3-(4'-Sulfo)benzylidenebornan-2-one and 58030-58-6                          salts                                                                        14 3-(4'-Methyl)benzylidenebornan-2-one 36861-47-9                            15 3-Benzylidenebornan-2-one 16087-24-8                                       16 1-(4'-Isopropylphenyl)-3-phenylpropane-1,3- 63260-25-9                      dione                                                                        17 4-Isopropylbenzyl salicylate 94134-93-7                                    18 2,4,6-Trianiline(o-carbo-2'-ethylhexyl-1'-oxy)- 88122-99-0                  1,3,5-triazine                                                               19 3-4-Imidazolylacrylic acid and its ethyl 104-98-3*                          ester                                                                        20 Ethyl 2-cyano-3,3-diphenylacrylate 5232-99-5                               21 2'-Ethylhexyl 2-cyano-3,3-diphenylacrylate 6197-30-4                       22 Menthyl o-aminobenzoate or: 134-09-8                                        5-methyl-2-(1-methylethyl)                                                    2-aminobenzoate                                                              23 Glyceryl p-aminobenzoate or: 136-44-7                                       1-glyceryl 4-aminobenzoate                                                   24 2,2'-Dihydroxy-4-methoxybenzophenone 131-53-3                               (dioxybenzone)                                                               25 2-Hydroxy-4-methoxy-4-methylbenzophenone 1641-17-4                          (mexonone)                                                                   26 Triethanolamine salicylate 2174-16-5                                       27 Dimethoxyphenylglyoxalic acid or:                                           Sodium 3,4-dimethoxyphenylglyoxalate                                         28 3-(4'Sulfo)benzylidenebornan-2-one and 56039-58-8                           its salts                                                                  ______________________________________                                    

Mention should also finally be made of micronized pigments such astitanium dioxide and zinc oxide.

The compounds to be used according to the invention are, as a rule,distinguished by a particularly high absorbance in the UV-A radiationregion. They are also readily soluble in cosmetic oils and can easily beincorporated into cosmetic formulations. The emulsions prepared with thecompounds I are particularly distinguished by their high stability, thecompounds I themselves by their high photostability, and theformulations prepared with I by their pleasant sensation on the skin.

U.S. Pat. No. 3,270,045 (1966) discloses the use of compounds of theformula ##STR4## where AR is an aromatic radical and X₁ is also analkoxy radical, as light stabilizers for organic materials which arealtered by UV radiation, especially plastics. Among the large number ofsubstances to be stabilized against UV radiation, such as plasticmaterials, sheets, foamed materials, whose surface is to be protected,also mentioned are "polishes, creams, lotions and the like". However,the skilled worker is unable to derive the teaching of the presentinvention from the complete context of this patent, ie. (a) to use thesecompounds as sunscreen agents for the human skin, (b) to make aselection in respect of UV-A absorbers and (c) to use these incombination with compounds which absorb in the UV-B region and are knownper se for cosmetic formulations.

This is all the more true since this reference is from 1966 and, asexplained at the outset, to date no stable UV-A absorbers have beenavailable for cosmetic application; on the contrary, the development hasbeen in the direction of external stabilization of UV-A absorbers whichare unstable on their own.

PREPARATION EXAMPLE 1

General method:

0.2 mol of alkylated benzophenone in 200 ml of heptane is mixed with anequimolar amount of malonitrile and 20 ml of a catalyst mixtureconsisting of amonium acetate/glacial acetic acid (molar ratio 1:4) andrefluxed with a water trap for 20 h. Each hour during the reaction, afurther 3 ml of the catalyst mixture are added. Subsequently theremaining catalyst is removed at about 50° C. and cooled to roomtemperature. The products precipitate. This is followed by filtrationwith suction and crystallization several times from ethyl acetate.Products which result as an oil are purified on a silica gel column withmethylene chloride as eluent (yield: 35%). Table 1 shows the individualsubstances prepared.

                  TABLE 1                                                         ______________________________________                                                                max.                                                    Com-  [nm]                                                                    pound  (CH.sub.2 CL.sub.2  m.p.                                               No. Structure [sic]) E.sub.1.sup.1 [° C.]                            ______________________________________                                          1                                                                                                                    360 470 64                                                                  -66                                       - 2                                                                                                                 360 630 80-82                           - 3                                                                                                                 344 730 90-94                           - 4                                                                                                                 346 460 oil                          ______________________________________                                    

General method for producing emulsions for cosmetic purposes

All the oil-soluble ingredients are heated to 85° C. in a stirredvessel. When all the ingredients have melted and are present in theliquid phase, the aqueous phase is incorporated with homogenization. Theemulsion is cooled to about 40° C. with stirring, is perfumed,homogenized and then cooled to 25° C. with continuous stirring.

FORMULATIONS EXAMPLE 2

Composition for lip protection

    ______________________________________                                        ad 100      Eucerinum anhydricum                                                10.00   Glycerol                                                              10.00  Titanium dioxide                                                       0.5-10 Compound of Table 1, No. 2                                             8.00 Octyl methoxycinnamate                                                   5.00 Zinc oxide                                                               4.00 Castor oil                                                               4.00 Pentaerythrithil stearate/caprate/caprylate                               adipate                                                                      3.00 Glyceryl stearate SE                                                     2.00 Beeswax                                                                  2.00 Microcrystalline wax                                                     2.00 Quaternium-18 bentonite                                                  1.50 PEG-45/dodecyl glycol copolymer                                        ______________________________________                                    

EXAMPLE 3

Composition for sunblocker with micropigments

    ______________________________________                                        ad 100        Water                                                             10.00   Octyl methoxcinnamate                                                 6.00 PEG-7-hydrogenated castor oil                                            6.00 Titanium dioxide                                                         0.5-10 Compound of Table 1, No. 4                                             5.00 Mineral oil                                                              5.00 Isoamyl p-methoxycinnamate                                               5.00 Propylene glycol                                                         3.00 Jojoba oil                                                               3.00 4-Methylbenzylidene camphor                                              2.00 PEG-45/dodecyl glycol copolymer                                          1.00 Butyl methoxydibenzoylmethane                                            1.00 Dimethicone                                                              0.50 PEG-40-hydrogenated castor oil                                           0.50 Tocopheryl acetate                                                       0.50 Phenoxyethanol                                                           0.20 EDTA                                                                   ______________________________________                                    

EXAMPLE 4

Fat-free gel

    ______________________________________                                        ad 100    Water                                                                 8.00 Octyl methoxycinnamate                                                   7.00 Titanium dioxide                                                         0.5-10 Compound of Table 1, No. 2                                             5.00 Glycerol                                                                 5.00 PEG-25 PABA                                                              1.00 4-Methylbenzylidene camphor                                              0.40 Acrylate C10--C30 alkyl acrylate crosspolymer                            0.30 Imidazolidinyl urea                                                      0.25 Hydroxyethyl cellulose                                                   0.25 Sodium methylparaben                                                     0.20 Disodium EDTA                                                            0.15 Fragrance                                                                0.15 Sodium propylparaben                                                     0.10 Sodium hydroxide                                                       ______________________________________                                    

EXAMPLE 5

Sun cream (SPF 20)

    ______________________________________                                        ad 100        Water                                                             8.00 Octyl methoxycinnamate                                                   8.00 Titanium dioxide                                                         6.00 PEG-7-hydrogenated castor oil                                            0.5-10 Compound of Table 1, No. 2.                                            6.00 Mineral oil                                                              5.00 Zinc oxide                                                               5.00 Isopropyl palmitate                                                      5.00 Imidazolidinyl urea                                                      3.00 Jojoba oil                                                               2.00 PEG-45/dodecyl glycol copolymer                                          1.00 4-Methylbenzylidene camphor                                              0.60 Magnesium stearate                                                       0.50 Tocopheryl acetate                                                       0.25 Methylparaben                                                            0.20 Disodium EDTA                                                            0.15 Propylparaben                                                          ______________________________________                                    

EXAMPLE 6

Sun cream water-resistant

    ______________________________________                                        ad 100        Water                                                             8.00 Octyl methoxycinnamate                                                   5.00 PEG-7-hydrogenated castor oil                                            5.00 Propylene glycol                                                         4.00 Isopropyl palmitate                                                      4.00 Caprylic/capric triglyceride                                             0.5-10 Compound in Table 1, No. 3                                             4.00 Glycerol                                                                 3.00 Jojoba oil                                                               2.00 4-Methylbenzylidene camphor                                              2.00 Titanium dioxide                                                         1.50 PEG-45/dodecyl glycol copolymer                                          1.50 Dimethicone                                                              0.70 Magnesium sulfate                                                        0.50 Magnesium stearate                                                       0.15 Fragrance                                                              ______________________________________                                    

EXAMPLE 7

Sun milk (SPF 6)

    ______________________________________                                        ad 100        Water                                                             10.00   Mineral oil                                                           6.00 PEG-7-hydrogenated castor oil                                            5.00 Isopropyl palmitate                                                      3.50 Octyl methoxycinnamate                                                   0.5-10 Compound in Table 1, No. 2                                             3.00 Caprylic/capric triglyceride                                             3.00 Jojoba oil                                                               2.00 PEG-45/dodecyl glycol copolymer                                          0.70 Magnesium sulfate                                                        0.60 Magnesium stearate                                                       0.50 Tocopheryl acetate                                                       0.30 Glycerol                                                                 0.25 Methylparaben                                                            0.15 Propylparaben                                                            0.05 Tocopherol                                                             ______________________________________                                    

We claim:
 1. A sun-screen cosmetic formulation for protecting the humanskin from the sun's rays which comprises: a cosmetically suitablecarrier, at least one compound of the formula ##STR9## where R¹ and R²are identical or different straight-chain or branched aliphatic orcycloaliphatic radicals which are in the para and/or ortho position andhave 1 to 18 carbon atoms, and where R¹ may additionally be hydrogenatom, and where furthermore n is 1 or 2, as UV-A filters and at leastone compound which absorbs the sun's rays in the UV-B region.
 2. Acosmetic formulation as defined in claim 1, which contains at least onecompound of the formula I wherein the aliphatic radicals in the positionof R¹ and R² are identical or different straight-chain or branched alkylradicals having 1 to 18 carbon atoms, in which the alkyl chain can beinterrupted by oxygen atoms, and where R¹ can also be hydrogen.
 3. Acosmetic formulation as defined in claim 1, wherein the aliphaticradicals in the position of R¹ and R² are identical or differentbranched alkoxy radicals which are in the para position and have 3 to 12carbon atoms, and n is in each case 1, and R¹ can additionally behydrogen.
 4. A sunscreen-containing cosmetic formulation as defined inclaim 1, wherein the cosmetically suitable carrier comprises at leastone oil phase.